The presence of pharmaceutical compounds in Surabaya rivers: potential sources and correlation with other water quality parameters

Recently identified compounds and chemicals that are harmful to the environment and pose a major risk to human health, known as emerging pollutants (EPs), are receiving increasing attention today. The main basis for this study is the absence of studies that discuss the presence of anti-inflammatory and anti-pain medicines in river water in Surabaya. Based on the study results, it was found that the overall average paracetamol concentration was 333 μg/L in Mas River and 430 μg/L in Surabaya River. Meanwhile, the ibuprofen concentration was not detected at all sampling points. This can be caused by the levels of ibuprofen, which are very small or below the detection limit. River water quality standards are regulated in Appendix VI of Government Regulation of the Republic of Indonesia Number 22 of 2021. On average, other water parameters that were also monitored, namely BOD, COD, nitrate, and phosphate, exceed the class II quality standards. Meanwhile, the pH and temperature parameters are within the class II quality standards range. Further research is needed to determine the presence of EPs in Surabaya rivers. This research can be a useful reference for further research.


Introduction
The existence of surface water as a support for human life is very important.Water is needed by living things for their survival, starting from drinking water, cleaning activities, and habitat for aquatic biota.One example of surface water that is widely utilized by humans is rivers.A river is a flow of water that forms a network of grooves on the earth's surface and flows continuously from upstream or source to downstream or estuary [1].The river is a water source that is easy to reach, which makes it the main water source for raw water supply.The quality and quantity of river water must be maintained to prevent human activities from polluting river water.The activities of humans that contribute to water quality and quantity can be in the form of agricultural activities, industrial activities, household activities, and fisheries activities [2].
River water problems that often occur in Indonesia are river water pollution.Water pollution can occur when substances that potentially degrade the quality of water are discharged into water bodies.1307 (2024) 012017 IOP Publishing doi:10.1088/1755-1315/1307/1/012017 2 Water pollution can be described as the appearance of living things, substances, energy, and/or other components in water by human activities so that it exceeds the established water quality standards.The water quality could decrease to a certain level, which causes water to no longer function in accordance with its designation [3].
With its role as a support for human life, the river's quality and quantity are essential to consider.For this reason, a standard is required to monitor river water quality.The standards are regulated in the river water quality standards in Appendix VI of Government Regulation Number 22 of 2021.Water quality standards are the limits or levels of living things, substances, energy, or components that exist or must exist and/or pollutant elements that are tolerated in water [3].
Micropollutants are also known as emerging pollutants, which means pollutants that are not regularly observed but have the potential to enter the environment and cause impacts on human health and ecological impacts.Micropollutants can be classified into pharmaceuticals, personal care products, industrial chemicals, disinfection products, toxic substances from algae, and biocidal organisms [4].Micropollutants most commonly found in aquatic areas include microplastics, pharmaceutical and personal care products (PPCSs), synthetic hormones, and human hormones [5].
Many advances have occurred in meeting human needs in the last few centuries.These needs cannot be separated from the use of chemicals.For example, the household sector uses soap, shampoo, and detergent.In addition, the agricultural sector uses fertilizers and pesticides.And the industrial sector, one of which uses chemicals to produce medicines.Wastewater generated by the pharmaceutical industry comes from equipment washing activities to the process of making medicines [6].Compounds and chemicals that have recently been identified as harmful to the environment and pose a significant risk to human health, known as emerging pollutants (EPs), are receiving increasing attention today.This study addresses the presence of several EP compounds in surface water in Surabaya and analyzes their impact on river quality.

Sample Collection
Water samples were collected between 06.00 and 09.00 am and between 02.00 and 05.00 pm for three consecutive days.According to the Krejcie Morgan sample period calculation using the average rainy day of Surabaya City, the sampling should be done for 9 days [7].Determination of the amount of sampling time used using the purposive sampling method.This method is carried out by considering certain things, such as research time, limited human resources, and costs incurred during the study.For this study, sampling was only carried out for three consecutive days.Determination of this sampling method aims to make the samples taken provide accurate data.
In this study, three sampling points were determined, namely on the right and left banks of the river.Sampling at these three points focuses on the location of the discharge source (outlet) in Mas River (Kali Mas) and Surabaya River (Kali Surabaya).This is because pollutant sources are not only sourced from residential activities, so sampling with three points in the research area represents the pollution condition in the specific area around the Mas River and Surabaya River segments.The sampling points are presented in Figure 1 and Figure 2.

Sample Analysis
The data obtained from measuring and testing water sample parameters will then be analyzed.The results and discussion of the data analysis include: 1. Concentration analysis of river water quality parameters (emerging pollutants, BOD, COD, and nutrients) using graphs that compare the results of each predetermined sample point.2. Analyzing the types of pollutant sources in the Surabaya River segment assessed through the identification of activities along the Surabaya River.3. Processing of primary and secondary water quality parameter measurement data.4. Correlation analysis between emerging pollutants parameters and water quality parameters (BOD, COD, and nutrients).
Samples of paracetamol, ibuprofen, BOD, COD, nutrients (N and P), pH, and temperature were analyzed in accordance with the standard methods specified.The methods used in this study are presented in Table 1

Pharmaceutical Compound
Pharmaceutical products or drugs are components commonly used in modern and traditional medicine.Pharmaceutical products are widely used both by individuals as medicines and agribusiness products to support the health and growth of livestock.Pharmaceutical products consist of drugs prescribed by doctors, drugs sold over the counter in pharmacies, and medicines for animals [8].
Pollutants from pharmaceutical products can be categorized into antibiotics, non-steroidal antiinflammatory drugs (NSAIDs), anticonvulsants or anti-seizures, and stimulants [8].Pharmaceutical product pollutants are able to produce resistant bacteria and alter the metabolic system of living things, thus making them harmful to the receiving environment [9].
Ibuprofen is an analgesic or anti-inflammatory compound that is commonly used to relieve symptoms of arthritis, rheumatism, pain, and fever.Ibuprofen is one of the basic medicines in the pharmaceutical world that are listed in the "Essential Drug List" by the World Health Organization (WHO).For this reason, its production is carried out massively throughout the world.Ibuprofen has the chemical formula C13H18O2 [10].Figure 3 presents the compound structure of ibuprofen.Ibuprofen is not only found in wastewater treatment systems, but also in several water bodies such as groundwaters, rivers, lakes, and coastal areas [11].The existence of ibuprofen in water bodies can be caused by the disposal of medicines in rivers and water bodies, and wastewater from the pharmaceutical industry.In addition, the presence of ibuprofen in water bodies can also be caused by the discharge of human feces and urine into water bodies.Most of the components of medicines are not metabolized and absorbed completely.It will be secreted through feces and urine as metabolites or unchanged components [12].
Ibuprofen was detected in surface and sediments, soil, and the agricultural sector [13].Prolonged exposure to ibuprofen in aquatic biota can cause chronic effects such as cytotoxic effects resulting in cell damage, genotoxic effects resulting in damage to genetic material in DNA, cells experiencing high oxidative stress, and adverse effects on growth and reproduction rates.
Several studies were conducted in multiple countries to determine the concentration of ibuprofen in surface water.Table 2 presents the detection results of ibuprofen concentrations in multiple countries.Paracetamol or acetaminophen is one of the anti-inflammatory drugs that functions as a pain reliever (analgesic) and fever reliever (antipyretic).Paracetamol has the compound formula C8H9NO2 with the following compound structure, presented in Figure 4.  Paracetamol is one of the most commonly used drugs and a drug that can be used without a prescription.Due to the wide use of paracetamol, the presence of paracetamol can be detected in wastewater, surface water, sludge, and groundwater.The existence of paracetamol in water is due to the content of paracetamol in the body is not completely absorbed by metabolism by humans, residues from the pharmaceutical industry, and agriculture [21].Paracetamol has the following characteristics Apart from being a pain reliever, paracetamol can function as a medicine to treat minor illnesses such as headaches.The increasing use of paracetamol has resulted in the waste of this type of medicine that can be found in surface water such as river water.With the presence of paracetamol in the water, organisms such as fish in the water will be disturbed and affect the main ecosystem of the water.The tissue (histological) and anatomical (hematological) conditions of fish will be disturbed, and fish can experience functional abnormalities from cells that have decreased from normal function [23].
In Indonesia, previous studies on pharmaceutical parameters such as paracetamol have been conducted in the waters of Jakarta Bay.In four areas in Jakarta Bay where sampling was conducted, two areas containing paracetamol were detected, namely in the Angke area and the Ancol area.The highest concentration of paracetamol was detected in Angke at 0.61 µg/L.While in the Ancol area, the concentration of paracetamol was 0.42 µg/L.The paracetamol content in both areas of Jakarta Bay showed concentrations 12 to 18 times higher among countries that have detected paracetamol in previous water areas.In the coastal waters of Brazil, the detected paracetamol concentration was 0.034 µg/L.The north coast of Portugal reported paracetamol concentrations ranging from 0.051-0.584µg/L with an average of 0.095 µg/L.The Ancol and Angke areas that detected the highest paracetamol were caused by domestic and industrial waste as well as the surrounding residential and commercial areas.As a result of paracetamol contamination with a concentration of 0.04 ng/L in waters, it causes potential damage to shellfish, fish mortality, hypoxia, eutrophication to toxic algae blooms, and reduced fish populations [24].

Result and Discussion
In this study, water quality data of Surabaya River and Mas River were obtained from direct sampling to determine the quality of river water.Sampling was conducted for three consecutive days on [16][17][18] March 2023 starting between 06.00-09.00am and 02.00-05.00pm.The process was carried out using a water sampler tool that was inserted into the water with a depth of 20-30 cm from the surface water level.This is done so that the water taken for the analysis process is not only from the surface, but the deeper part of the river can be reached so that the sample becomes more representative.After that, the water was put into one liter and 250 mL plastic sample bottles for laboratory testing.Samples were preserved using dry ice until the lab testing process was carried out.
Based on the results of the analysis, it will then be compared with the river water quality standards of Indonesia's Government Regulation Number 22 of 2021 Appendix VI.   [25].Microorganisms in the water can degrade the pollutant load if the pH value in the water is in accordance with the specified range, so that microorganisms in the water can survive [26].Temperatures will affect the growth of plankton and other aquatic biota in the water body.In addition, temperatures also affect the level of oxygen solubility.The higher the water temperature, the lower the oxygen solubility.The highest temperature recorded in the water sample was 23.2 ºC and the lowest temperature was 22.8 ºC.The temperature value of water quality standards for class II is at a deviation of 3 [3], which means that the maximum temperature in water is 28 ºC and the minimum temperature is 22 ºC.Thus, all recorded temperature data in this study are within the range of the government regulation.BOD or Biological Oxygen Demand is the amount of dissolved oxygen content in water required by microorganisms to decompose organic matter.BOD is one of the key parameters used to determine the quality of water bodies.The highest BOD value in the water sample was on March 18, 2023 at Surabaya River point 3 in the noon was 45 mg/L, and the lowest BOD was on March 18, 2023 at Mas River point 2 in the noon was 2 mg/L.This can be due to a reason that caused by agricultural and industrial activities, land-use changes, and increased domestic activities of communities around water bodies.The main sources associated with BOD include wood and leaf debris, animal feces, dead animals and plants, animal feedlots, effluents from paper and pulp mills, and poorly functioning septic systems.Other than that, water temperature also plays important role in higher BOD level.As the temperature of water increases, the rate of bacterial decomposition also increases, leading to higher BOD levels.The BOD value of class II water quality standards is 3 mg/L [3].

Figure 8. COD Test Results
The highest COD value in the water sample was on March 18, 2023 at Surabaya River point 3 in the noon was 84 mg/L, and the lowest BOD was on March 18, 2023 at Mas River point 2 in the noon was 4 mg/L.This can be due to a reason that caused by the presence of organic matter, such as decaying plant matter, human waste, or industrial effluent, same as BOD level.COD increases as the concentration of organic material increases.Other than that, high COD can be caused by various factors, including the discharge of municipal wastewater, industrial processes that create water high in COD/BOD, and agricultural runoff.The COD value of class II water quality standards is 25 mg/L [3].Nitrate comes from ammonia that enters the water mainly from domestic waste pollutants such as fertilizers.Based on Figure 9, the highest nitrate level recorded in the water samples was on 18 March 2023 at Mas River at point 3 in the noon was 3 mg/L and the lowest nitrate level was on 16 March 2023 in Surabaya River at point 1 in the morning was 0.04 mg/L.The nitrate quality standard for class II water is 10 mg/L [3].The low nitrate levels in the test results are due to the fact that around the sampling area there are no agricultural areas or rice fields, so it is far from nitrate pollutant sources, namely agricultural fertilizers and agricultural waste [27].The highest phosphate level read in the water samples was on 18 March 2023 in Surabaya River was 12.26 mg/L and the lowest phosphate level was on 16 March 2023 at Mas River point 2 in the morning was 1.67 mg/L.The phosphate quality standard for class II water is 0.2 mg/L [3].Based on Figure 10, it shows that all phosphate levels at each point exceed the class II water quality standards, which means that the phosphate parameter requires special attention so that the waters can be used properly in accordance with class II water quality standards and not pollute the aquatic environment.High phosphate levels can be caused by pollutant sources originating from domestic activities such as detergent waste and there are fecal contaminants from the surrounding community that enter the waters [28].

Ibuprofen and Paracetamol Analysis Results
Data of ibuprofen and paracetamol parameters in Sungai Surabaya and Mas River Surabaya were obtained by sampling for three consecutive days on March 16, 2023, March 17, 2023, and March 18, 2023.The quality analysis of ibuprofen parameter was conducted through liquid phase using HPLC with wavelength (λ) 222.4 nm and paracetamol parameters were carried out through the liquid phase using HPLC with a wavelength (λ) of 246.4 nm.Then the determination of ibuprofen and paracetamol levels was carried out using calculations with calibration curves that have been obtained.The results of the calculation of ibuprofen levels are presented in Table 4 below.Based on Table 4, ibuprofen levels were only detected at point 3 of Surabaya River on March 16, 2023 in the morning at 1.206 mg/L.However, at other sampling points, the levels are below the detection limit (shown in negative values).Low levels of ibuprofen readings or below the detection limit can be caused by ibuprofen's low solubility in water.Ibuprofen has the characteristic of being difficult to dissolve in water.The solubility of ibuprofen in water is 11 μg/mL.The solubility of ibuprofen is greater in organic solvents such as alcohol, ethanol, methanol, acetone, and dichloromethanes [29].In this study, the analysis of ibuprofen levels by HPLC was carried out on the liquid phase of the water sample without conduction solid phase extraction.When looking at the low solubility of ibuprofen in water, this could be one of the causes of the low levels of ibuprofen read on HPLC.In Table 5, the calculation results of paracetamol levels in Surabaya River and Mas River are presented.5, paracetamol levels on 16-18 March 2023 fluctuates.At the sampling location in Surabaya River, the highest paracetamol level was on 16 March 2023 at point 1 in the morning at 1.241 mg/L.While the smallest paracetamol level was on 18 March 2023 at point 2 in the morning at 0.149 mg/L.The average paracetamol level obtained during the 3-day sampling was 0.43 mg/L.While at the sampling location in Mas River Surabaya, the highest paracetamol level was on 17 March 2023 at point 2 in the morning at 0.506 mg/L.While the smallest paracetamol level was on 18 March 2023 at point 2 in the afternoon at 0.157 mg/L.The average paracetamol level obtained during the 3-day sampling was 0.333 mg/L.The levels of paracetamol found in Jakarta Bay were 0.42 µg/L and 0.61 µg/L.Compared to the average paracetamol level found in Mas River Surabaya, which was 0.333 mg/L or 333 µg/L, the paracetamol level found in Mas River Surabaya was greater.The level of paracetamol detected in the surface water represents 5% of the entire dose consumed by humans and excreted as paracetamol [24].Paracetamol that is excreted through urine and feces in humans is only excreted 1-3% as paracetamol and exits through the human excretory system [30].
In this study, multiple linear correlation analysis was conducted between paracetamol variables (dependent variable) and water quality parameters (independent variable) in Surabaya River and Mas River.This correlation is done to determine how much influence the independent variable has on the dependent variable.The results of the correlation in Surabaya River and Mas River can be seen in Table 6 and Table 7 Based on the results of the analysis that has been done, the value of Sig.F Change in Surabaya River and Mas River is 0.201 and 0.122.Because the value of Sig.F Change in both locations >0.005, it can be concluded that the variables of Nitrate (X1), Phosphate (X2), BOD (X3), COD (X4), Temperature (X5), and pH (X6) have no correlation or no significant relationship to the variable paracetamol (Y).This means that there is no evidence strong enough to prove that these variables are interconnected or have a correlation.
In general, there is no correlation between paracetamol parameters and water quality parameters.This is because water quality parameters are complex and come from various sources [31].Paracetamol is a pharmaceutical compound that is different from water quality parameters which are organic and non-organic compounds in water.Hence, in this case, it is necessary to conduct more in-depth research to determine the correlation between paracetamol parameters and water quality parameters.While ibuprofen correlation with water quality parameters cannot be determined.Due to ibuprofen parameter is below the detection limit, the amount cannot be determined.Thus, it can be assumed that ibuprofen was not detected in Surabaya River and assumed to be 0.
The presence of ibuprofen in water bodies can be caused by the disposal of medicines in rivers and water bodies, and wastewater from the pharmaceutical industry.In addition, the presence of ibuprofen in water bodies can also be caused by the discharge of human feces and urine into water bodies [12].
Ibuprofen identified in water bodies can come from several activities such as the excretion of the consumption of drugs containing ibuprofen by the community.This is because ibuprofen is a type of drug that can be traded freely in pharmacies without a doctor's prescription and made it easy for people to buy it as an anti-pain.In addition, ibuprofen can also be sourced from the pharmaceutical industry, hospitals, and other health facilities.Figure 11 presents the identification of pollutant sources around the sampling point in Surabaya River.Based on Figure 11, there are several large and medium-sized hospitals that have the potential to produce ibuprofen compound waste.Although these hospitals have WWTPs to treat their wastewater.However, it is known that conventional WWTPs are not specifically designed to remove emerging pollutants.
In the waters of Mas River Surabaya, potential sources of pollutants can come from residential activities around the downstream of Mas River Surabaya.The settlements located around the downstream of Mas River produce waste from domestic activities such as urine and feces.Apart from residential activities, potential sources of paracetamol contaminants can come from pharmacies and health facilities such as clinics.The identification of pollutant sources was carried out within a radius of 1 km from the sampling point with the aim of focusing the coverage on the area around the sampling point.The following is the flow of paracetamol pollutants to Mas River Surabaya that is presented in Figure 12.Based on Figure 12, the sampling point in this study is in the downstream of Mas River which flows from Jagir River fragment to the north coast of Surabaya City.Pollutant sources that cause potential paracetamol pollution in the downstream of Mas River Surabaya can come from domestic activities, health facilities and industries.The source of potential paracetamol pollution from domestic activities comes out through urine and feces and flows to the nearest waters in the upstream area, then can be carried and accumulated to the downstream area which is detected at the sampling point.

Conclusion
Based on the results of the study, it cannot be confirmed that the source of ibuprofen and paracetamol contaminants in Surabaya River and Mas River Surabaya came from domestic activities and health facilities, so further research is needed to find out more specific sources of potential contaminants.However, based on the literature study conducted, there is a potential spread of ibuprofen and paracetamol compounds through wastewater outlets from residential areas, pharmacies, hospitals, health centers, and other health facilities.The ibuprofen concentration is below the detection limit, so the amount cannot be determined.The introduction of solid phase extraction can also be considered before quantification using HPLC.On the other hand, the paracetamol concentration is detected both in Surabaya River and Mas River with the highest amount detected at 1.241 mg/L.Based on this study results, no correlation was found between ibuprofen and paracetamol parameters with water quality parameters.To the best of our knowledge, this study is the first to discuss the presence of paracetamol in Surabaya rivers.Hence, further research is needed.Conventional water quality parameters that meet class II water quality standards based on this study are pH, temperature, and nitrate.Meanwhile, BOD, COD, and phosphate parameters still exceed class II water quality standards.

Figure 12 .
Figure 12.Potential Paracetamol Pollutant Sources in the Downstream of Mas River Surabaya

Table 1 .
below.Methods Used for Analysis

Table 2 .
Previous Research on Ibuprofen

Table 3 .
Table 3 presents the river water quality standards of Government Regulation Number 22 of 2021 Appendix VI based on its class.River Water Quality Based on Its Class (Source: Government Regulation Number 22 of 2021 Appendix VI, 2023) 3.1 pH

Table 4 .
Ibuprofen Levels in Surabaya River and Mas River

Table 5 .
Paracetamol Levels in Surabaya River and Mas River

Table 6 .
. Correlation Test Results at Surabaya River

Table 7 .
Correlation Test Results at Mas River